High frequency stimulation

Long-term potentiation (LTP) is a synaptic plasticity phenomenon that corresponds to an increase in the synaptic strength (increase in the post-synaptic response observed for the same stimulation of the presynaptic terminals) observed after a high frequency stimulation (tetanus) of the afferent fibres. This increased response is still observed hours and even days after the tetanus. The phenomenon is often observed at glutamatergic synapses and involves, in most cases, the activation of the V-methyl D-aspartate (NMDA) subtype of ionotropic glutamate receptors. 

High frequency fatigue or fatigue during continuous high frequency stimulation seems to be mainly due to impaired propagation of the stimulating impulse in the T-tubular system. 

LSnnergren, J. Westerblad, H. (1986). Force and membrane potential during and after fatiguing, continuous high-frequency stimulation of single Ae/topus muscle fibers. Acta Physiol. Scand. 128, 359-368. 

The release of some peptides may differ from that of other transmitters, depending on the firing rate of the neurons. The large vesicles needed to store a peptide may need a greater rate of depolarisation for membrane fusion and release of the contents. In the salivary gland the release of vasoactive intestinal polypeptide requires high-frequency stimulation whereas acetylcholine is released by all stimuli. Due to the complexities and problems of access to CNS synapses it is not known if the same occurs here but there is no reason why this should not. In sensory C-fibres a prolonged stimulus appears to be a prerequisite for the release of substance P. 

As with the biosynthesis of anandamide, the biosynthesis of 2-AG is also triggered by increases of intracellular calcium ions that result from neuronal activity. High frequency stimulation of neurons produced a fourfold increase of 2-AG accumulation compared with controls, and this was prevented by sodium ion channel blocking or removal of calcium ions (Stella, 1997). The concentration of 2-AG in depolarized neurons reached 1 to 2 pM, significantly higher than anandamide and sufficient to substantially activate CB1 (Stella, 1997). 

Thus, the mechanistic properties of the NMDA receptor can help account for the properties of temporal specificity, cooperativity, and associativity of LTP. They can also explain why both high-frequency stimulation (100 Hz) and pairing low-frequency stimulation with postsynaptic depolarization can induce LTP. The occurrence of presynaptic activity followed by postsynaptic activity determines a temporal sequence and specificity. To generate sufficient depolarization in the postsynaptic cell to expel Mg2+ from NMDAR channels usually requires cooperative depolarization at many synapses. Moreover, the requirement of postsynaptic depolarization also underlies associativity since the depolarization caused by the strongly activated synapses can relieve the Mg2+ blockade of the NMDA receptors on weakly activated synapses. 

Figurov A, Pozzo-Miller LD, Olafsson P et al. Regulation of synaptic responses to high-frequency stimulation and LTP by neurotrophins in the hippocampus. Nature 381 706-709,1996. 

Somlyo It is possible in smooth muscle preparations to do high frequency stimulation of nerves, and get a contraction that is abolished by TTX. This suggests that the transmitter does get to the smooth muscles. This is a physiological experiment. 

B. Long-term potentiation in the dentate gyrus recorded in vivo. The graph plots the early rising slope of the field excitatory postsynaptic potential (EPSP) in response to low frequency stimulation (700 pA, 100 ms, 0.05 Hz). Four trains of high frequency stimulation (700 pA, 82.5 ms, 400 Hz) were dehvered at time 0. This produced an immediate increase in the EPSP slope (post-tetanic potentiation) and a sustained relatively constant enhancement that lasted for at least 60 minutes. Representative traces are included below the graph. Note the obvious increase in size of the superimposed population spike (downward deflection). 

Vandewalle, V., van der Linden, C., Groenewegen, H.J., and Cae-maert, J. (1999) Stereotactic treatment of Gilles de la Tourette syndrome by high frequency stimulation of thalamus. Lancet 353 724. 

Pre-clinical work and neuroimaging suggest potential frequency-dependent effects of rTMS. Thus, higher frequencies may increase while lower frequencies may decrease brain metabolism (205). Clinically, repetitive, high frequency stimulation (i.e., >1 Hz or HF-rTMS) and repetitive, low frequency stimulation (i.e., 1 Hz or SF-rTMS), have been used. 

Urban, N. N., and Barrionuevo, G. (1996). Induction of hebbian and non-hebbian mossy fiber longterm potentiation by distinct patterns of high-frequency stimulation. J. Neurosci. 16, 4293-4299. 

Hartmann, M., Heumann, R., and Lessmann, V. (2001). Synaptic secretion of BDNF after high-frequency stimulation of glutamatergic synapses. EMBOJ. 20, 5887—5897. 

Garcia L., D Alessandro G., Bioulac B., Hammond C. High-frequency stimulation in Parkinson s disease more or less Trends in Neuroscience, 2005, 28, 209-216. Garenne A. and Chauvet G. A. A discrete approach for a model of temporal learning by the cerebellum in silico classical conditioning of the eyeblink reflex. / Integr Neurosci, 2004, 3,301-18. 

Rubin J. E. and Terman D. High frequency stimulation of the subthalamic nucleus eliminates pathological thalamic rhyth-micity in a computational model. J Comput Neurosci, 2004, 16, 211-235. 

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